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PMID: 8262046 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Promoter analysis of the gene encoding the I kappa B-alpha/MAD3 inhibitor of NF-kappa B: positive regulation by members of the rel/NF-kappa B family.

The EMBO journal ·Vol. 12 ·No. 13 ·1993-12-15 ·Pages 5043-9

Le Bail O, Schmidt-Ullrich R, Israël A

Abstract

In order to characterize the regulation of the gene encoding the I kappa B-alpha/MAD3 inhibitor of the transcription factor NF-kappa B, we have isolated a human genomic clone and sequenced the promoter of this gene. The MAD3 promoter exhibits a potential TATA element upstream of one of the two major transcription sites, and contains several potential NF-kappa B binding sequences, suggesting that the gene is positively regulated by members of this family. Transfection experiments demonstrate that the MAD3 promoter can be activated by various combinations of members of the rel/NF-kappa B family, as well as by phorbol esters and tumor necrosis factor. Specific deletion of one of the kappa B motifs, located 37 bp upstream of the TATA box, abolishes responses to PMA and TNF. This kappa B motif binds NF-kappa B (p50/relA), p50/c-rel and relA/c-rel heterodimers as well as KBF1 (p50 homodimer). These results help to explain the previously observed transient nature of the NF-kappa B response: following NF-kappa B activation, the expression of the inhibitor is increased, therefore the extent of nuclear translocation of the active complex is reduced, resulting in a decreased activation of its target genes.

MeSH Terms
Base Sequence Binding Sites Cloning, Molecular DNA-Binding Proteins/genetics Gene Expression Regulation/drug effects Genes Humans I-kappa B Proteins Molecular Sequence Data Mutagenesis, Site-Directed NF-KappaB Inhibitor alpha NF-kappa B/antagonists & inhibitors,genetics Oligodeoxyribonucleotides/chemistry Promoter Regions, Genetic Proto-Oncogene Proteins/genetics Proto-Oncogene Proteins c-rel Sequence Deletion Tetradecanoylphorbol Acetate/pharmacology Transcription Factor RelB Transcription Factors Tumor Necrosis Factor-alpha/pharmacology
Chemicals
DNA-Binding Proteins I-kappa B Proteins NF-kappa B NFKBIA protein, human Oligodeoxyribonucleotides Proto-Oncogene Proteins Proto-Oncogene Proteins c-rel RELB protein, human Transcription Factors Tumor Necrosis Factor-alpha NF-KappaB Inhibitor alpha Transcription Factor RelB Tetradecanoylphorbol Acetate
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Le Bail O
Unité de Biologie Moléculaire de l'Expression Génique, URA 1149 CNRS, Institut Pasteur, Paris, France.
Schmidt-Ullrich R
Israël A
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1993-12-15
Pages
5043-9
Language
English
Region
England
NLM ID
8208664
PMCID
PMC413764
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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